Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1974 and July 1987 the diagnosis of severe aplastic anaemia (SAA) was confirmed in 82 patients. Overall actuarial survival was 57% at 7 yr. Four patients recovered while receiving conventional therapy, and four died before treatment with antithymocyte globulin (ATG) or bone marrow transplantation (BMT) could be initiated. Nineteen patients (median age 19.6 yr) were treated with allogeneic BMT (11 as initial therapy, eight after ATG). Incidence of acute and chronic graft versus host disease was high, occurring in 14/16 and 4/11 patients at risk, respectively. Survival of BMT patients (18/19 transfused) was 32% at 7 yr. Of 63 patients treated with ATG, survival was 63% at 7 yr but decreased to 43% at 11 yr. The 2.5 yr survival following ATG was influenced by pretreatment disease severity (defined by percentage reticulocytes, granulocyte and platelet counts), age and--in patients under 45 yr of age--by sex. However, pretreatment disease severity was less in patients aged between 20 and 45 yr and in females. Concomitant androgen therapy, animal source of ATG, interval diagnosis--ATG (which was in general rather short) and aetiology did not influence survival. Thirty-four patients became transfusion independent for up to 26 months after ATG. A gradual increase in granulocyte and platelet counts could be observed over a period of many years, and 26 patients recovered to show a normal haemoglobin level, granulocytes greater than or equal to 1.0 X 10(9)/l and platelets greater than or equal to 100 X 10(9)/l). Late complications (paroxysmal nocturnal haemoglobinuria, myelodysplastic syndrome/acute leukaemia, hepatocellular carcinoma) were observed in nine patients who survived with autologous marrow function. Five died within 12 yr of initial therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acquired severe aplastic anaemia in adults--a single centre study with 13 years follow-up. 225 Jul 51

In the presence of aplastic anemia (AA), therapeutic choices should be determined while taking into account not only changes for immediate improvement, but also both the risks for late-occurring complications and the following quality of life. We report here data concerning a long-term clinical survey (5 to 18 years with a median of 12 years) including 156 nongrafted patients receiving androgen therapy; all patients were alive more than 5 years after diagnosis (40% of patients included at time of diagnosis in our multicentric analysis). Between the 5th and the 13th year follow-up, 21 patients died of various causes either related to AA or to its treatment: 12 of infection or hemorrhage secondary to pancytopenia (6 relapses and 6 that had never been improved; 2 with paroxysmal nocturnal hemoglobinuria [PNH]); 5 of leukemia; 1 of a non-Hodgkin's lymphoma; 2 of late side effects following transfusion (1 acquired immunodeficiency syndrome and 1 chronic B hepatitis); and a single case of myocardial infarction (the latter could possibly result of androgen therapy). Thirteen patients in total developed PNH (among which 10 had clinical symptoms including 2 deaths, and 3 exhibited only biologic abnormalities). Few long-term side effects of androgens could be noticed. Adult height was normal in patients treated during childhood and so was young women's fertility. No malignant hepatoma occurred. This survey allows the recording of late spontaneous hematologic improvement (between 5 and 10 years of evolution). This occurred in 50% of patients that had remained cytopenic 5 years after diagnosis. Although bone marrow stem cell concentration remained abnormal after 10 years of evolution. 85% of patients had a normal red blood cell count, 80% a normal polymorphonuclear count, and 66% a normal platelet count. All patients who did not show late complications had an excellent quality of life.
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PMID:Long-term (5 to 20 years) Evolution of nongrafted aplastic anemias. The Cooperative Group for the Study of Aplastic and Refractory Anemias. 225 96

Calvatic acid (p-carboxyphenylazoxycyanide) is an antibiotic containing an azoxycyano group that displays carcinostatic activity. In the present work it has been shown that in AH-130 hepatoma and K562 leukemia cells the antibiotic, at low concentration, decreases ornithine decarboxylase (ODC) levels. The change depends on two summative effects of the drug, impairment of overall protein synthesis and inhibition of enzyme activity. Some analogs of calvatic acid have been tested in order to gain more insight into the structure-activity relationship. The decarboxylated derivative phenylazoxycyanide proved to be more effective in reducing protein synthesis and ODC activity in the whole tumor cells. The rapidly growing K562 cells displayed high sensitivity to this compound. Calvatic acid analogs devoid of the cyano group were less effective on the same parameters.
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PMID:Effect of calvatic acid and its analogs on ornithine decarboxylase activity in tumour cells. 227 63

We studied the creatine kinase (CK) isoenzyme pattern in sera from 332 patients affected by hepatic cirrhosis and several neoplastic diseases (102 cirrhosis, 36 hepatocarcinoma, 16 metastatic liver tumor, 40 breast cancer, 18 other neoplastic diseases and 120 cases of leukemia or lymphoma) to evaluate both its diagnostic utility for cancer diagnosis and its power as a prognostic index. Type-2 macro CK (mitochondrial creatine kinase) was detected, with no statistical difference in cirrhosis (14%), hepatocarcinoma (16%), metastatic liver tumor (31%), breast cancer (5%) and other tumors (6%). It was not detected in any patient with leukemia or lymphoma. The presence of type-2 macro CK was unrelated to the stage of either cirrhosis or hepatocarcinoma, according to Child and Okuda, respectively, nor was it correlated to serum cytolytic enzyme levels or to gamma-globulin levels. In cirrhotics, type-2 macro CK was not linked to serum levels of the following tumor markers: alpha-fetoprotein, pseudouridine and gamma-glutamyltransferase isoenzymes complexed to low-density lipoprotein. In addition, the atypical band persisted in several patients with cirrhosis monitored for six months who did not show any evidence of evolution toward hepatocarcinoma. Thus, type-2 macro CK has poor diagnostic sensitivity for neoplastic diseases, and lacks prognostic value both in cirrhosis and neoplastic diseases.
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PMID:Serum type-2 macro-creatine kinase isoenzyme is not a useful marker of severe liver diseases or neoplasia. 228 11

Flow cytometry was used to detect fibrinogen (platelet associated fibrinogen: PAFbg) and fibronectin (PAFn) on the surface membrane of platelets in leukemia (9 cases), lung cancer (15 cases) and hepatoma (8 cases) patients (by one color analysis method), and simultaneously to investigate the binding of monoclonal anti-glycoprotein (GP) IIb/IIIa and anti-GP Ib antibodies (by two color analysis). All patient groups showed higher Fbg values than the normal control group, but no differences were found between patient groups. The values of Fbg and Fn showed a correlation, but the pattern of binding did not show a regular tendency in any patient group. There also was no significant correlation between Fbg values and the positive percentage of monoclonal anti-GPIIb/IIIa and anti-GPIb antibodies, and the binding of Fbg did not inhibit that of monoclonal antibody. The results suggest the following. 1. There are no differences in platelet activation in leukemia, lung cancer and hepatoma patients, and the degree of platelet activation is decided by the degree and the kind of stimulation. 2. The increase of both PAFbg and PAFn prove to the existence of activated platelet.
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PMID:[Analysis of adhesive proteins on the surface membrane of platelet in malignant neoplasm]. 232 78

Many hormonal, neurotransmitter, and sensory stimuli trigger the formation of inositol 1,4,5-trisphosphate, which in turn releases calcium from intracellular stores. We report here that inositol 1,4,5-trisphosphate-induced calcium release from saponin-permeabilized rat basophilic leukemia cells at 37 degrees C is markedly biphasic, in contrast with nearly monophasic release kinetics at 11 degrees C. Hepatoma, PC-12 neuronal cells, and several other cell types exhibit similar biphasic release at 37 degrees C. The biphasic kinetics are not due to degradation of inositol 1,4,5-trisphosphate or to increased Ca2(+)-ATPase pump activity. Biphasic calcium release was also seen when ATP was quenched to less than 0.4 microM by adding hexokinase and glucose, suggesting that phosphorylation is not involved. External calcium (100 nM-600 nM) range had little influence on the biphasic kinetics. Rapid-mixing experiments revealed that rapid efflux of calcium is followed in approximately 0.5 s by a 30-fold slower efflux. Most striking, successive additions of the same amount of inositol 1,4,5-trisphosphate induced short bursts of calcium release of similar size. This retention of responsiveness, which we term increment detection, may be a distinct mode of signal transduction. Like inactivation and adaptation, increment detection gives rise to transient responses to sustained stimuli. Systems exhibiting inactivation, adaptation, and increment detection differ in their responsiveness (none, partial, and full, respectively) to stepwise increases in stimulus intensity. Increment detection could be advantageous in generating receptor-triggered calcium oscillations.
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PMID:Transient calcium release induced by successive increments of inositol 1,4,5-trisphosphate. 233 24

A study on the oncolytic activity of the L-cysteine derivative L-cysteine, ethyl ester, S-(N-methylcarbamate) monohydrochloride (NSC 303861), revealed that the drug caused complete regression of the MX-1 human mammary tumor xenograft. The compound also exhibited moderate antitumor activity against murine leukemia P388 (T/C value of 169% at a daily dose of 400 mg/kg) and against M5076 sarcoma (T/C value of 135% at a daily dose of 600 mg/kg). The drug was inactive against B16 melanoma, Lewis lung, colon 38 and CD8F1 mammary carcinomas. The compound exhibited significant cytotoxicity against hepatoma 3924A cells in culture (LC50 = 6 microM). Studies on the mechanism of action revealed that the cytotoxicity of the drug could be partially abrogated by protecting hepatoma 3924A cells in culture with L-glutamine. At 6 h after injection of the compound (400 mg/kg) into rats bearing hepatoma 3924A, the pools of L-glutamine and L-glutamate in the tumor decreased to 33% and 71%, respectively, of control levels; the drug selectively inhibited the activities of L-glutamine-requiring enzymes of purine nucleotide biosynthesis, amidophosphoribosyltransferase, FGAM synthase, and GMP synthase, to 21%, 1%, and 69%, respectively, without significantly altering the activities of pyrimidine biosynthetic enzymes, carbamoylphosphate synthase II and CTP synthase. Measurement of the nucleotide concentrations further corroborated the actions of the drug on the purine nucleotide biosynthetic enzyme activities. Drug injection (400 mg/kg) in the hepatoma 3924A-bearing rats reduced the concentrations of IMP in the tumor to 52%, those of total adenylates to 52%, those of total guanylates to 57%, and those of NAD to 73%, without significantly perturbing the pyrimidine nucleotide pools. Studies on the mechanism of action of the L-cysteine derivative suggested that the compound behaved as an L-glutamine antagonist, selectively acting on the enzymes of purine nucleotide biosynthesis.
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PMID:Oncolytic activity and mechanism of action of a novel L-cysteine derivative, L-cysteine, ethyl ester, S-(N-methylcarbamate) monohydrochloride. 234 42

We studied the antitumor activity of newly synthesized bis(1-acyloxymethyl) derivatives of 4,4'-(1,2-ethanediyl)bis(2,6-piperazinedione) using i.p.-i.p. models of P388 leukemia and B16 myeloma. As a result, we found 4,4'-(1,2-ethanediyl)bis(1-isobutoxycarbonyloxymethyl-2,6-piperazi nedione) (MST-16) to possess considerable therapeutic activity. MST-16 showed not only marked life-prolonging effects in both P388 leukemia- and B16 melanoma-bearing mice but also a greater therapeutic ratio than did its parent compounds, ICRF-154 and ICRF-159. Further studies revealed that MST-16 has considerable therapeutic activity against a number of other tumors such as ascitic forms of L1210 leukemia, colon 26 adenocarcinoma, and MH-134 hepatoma and solid forms of B16 melanoma, Lewis lung carcinoma, colon 38 adenocarcinoma, and M5076 fibrosarcoma. These results suggest that MST-16 is very promising as an antitumor agent.
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PMID:Antitumor activity of MST-16, a novel derivative of bis(2,6-dioxopiperazine), in murine tumor models. 235 66

Cellular interaction and in vitro antitumor activity of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), were studied in relation to its physicochemical characteristics. MMC-D with cationic and anionic charges were examined. The cationic MMC-D was synthesized using a spacer, epsilon-aminocaproic acid and dextrans with molecular weights of 10,000, 70,000, or 500,000 [MMC(C6)Dcat]. The anionic MMC-D was synthesized using 6-bromohexanoic acid as a spacer and dextran with a molecular weight of 70,000 [MMC(C6)Dan]. Cellular adsorption was determined by measuring the concentration of the drug in the medium after incubation with three tumor cell lines, Ehrlich ascites carcinoma, L1210 leukemia, and AH66 ascites hepatoma cells. MMC(C6)Dcat was adsorbed more readily than MMC or MMC(C6)Dan on the tumor cell surface by an electrostatic force. The percentage of adsorption remained almost constant during the course of incubation and no significant difference was observed between the incubation at 4 degrees C and that at 37 degrees C. A corresponding increase in the amounts of MMC(C6)Dcat adsorbed on with higher molecular weights was noted, which conformed to Langmuir's adsorption isotherm. In vitro antitumor activity was evaluated using L1210 and EAC cell culture systems and human tumor colony forming assay. MMC(C6)Dcat showed growth inhibition essentially equal to that of MMC in continuous drug exposure experiments. In a 1-h drug exposure experiment, MMC(C6)Dcat with a molecular weight of 70,000 or 500,000 was more active than MMC, and a good correlation was observed between the effects of MMC(C6)Dcat and the extent of cellular interaction. These results show that cellular interaction played an important role in the manifestation of the antitumor effect of MMC-D and that these phenomena are governed by the physicochemical properties of macromolecular prodrugs, such as electric charge and molecular weight.
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PMID:Cellular interaction and in vitro antitumor activity of mitomycin C-dextran conjugate. 242 52

Recent progress in biotechnology has uncovered the presence of trace substances which participate in the immunological response between cancer and host; They are cytokines, monoclonal antibodies, and immunomodulating agents produced by effector cells which are called macrophage, NK cells and lymphocytes of cancer patients. Recent genetic engineering enables mass production of these substances, and their clinical application in treating human cancers is expected to take place in the near future. In this paper, the recent trend of cancer treatment, using various cytokines are briefly introduced, namely interferon, interleukin-2, tumor necrosis factor and colony stimulating factor. Although IL-2 is effective for the activation of T-lymphocyte, intravenous injection of IL-2 is not so effective for treatment of cancer-patients. On the other hand, IL-2-activated killer cells (LAK cells) are potent effectors of adoptive immunotherapy in advanced cancer patients. The clinical study was conducted in 25 patients with advanced carcinomas. Therapeutic efficacy was obtained in patients for whom local transfer was undertaken rather than systemic administration. Tumor necrosis factor, a cytotoxin derived from macrophages shows much promise for application in cancer therapy because of its marked antitumor effects and its high specificity to tumors. Clinical study was performed on leukemia patients who showed marked decreases of percentage of leukemic cells in peripheral blood. Moreover, local injection of TNF was very effective for the decrease of tumor size in patients with hepatoma and subcutaneous tumor. In addition, to clinical results using CSF and interferon are reported.
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PMID:[Recent trends in cancer treatment using cytokines]. 247 55


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